Therapeutic ISCOMATRIX ™ adjuvant vaccine elicits effective anti-tumor immunity in the TRAMP-C1 mouse model of prostate cancer

In this study, we examine the effectiveness of a therapeutic cancer vaccine that combines the ISCOMATRIX ™ adjuvant (ISCOMATRIX) with the Toll-like receptor 3 agonist, polyinosinic–polycytidylic acid (Poly I:C), and Flt3L, FMS-like tyrosine kinase 3 ligand. We employed the TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) model of prostate cancer and the self-protein mPAP (prostatic acid p hosphatase) as the tumor antigen. ISCOMATRIX™–mPAP–Poly I:C–Flt3L was delivered in a therapeutic prime-boost regime that was consistently able to achieve complete tumor regression in 60% of animals treated and these tumor-free animals were protected upon rechallenge. Investigations into the underlying immunological mechanisms contributing to the effectiveness of this vaccine identified that both innate and adaptive responses are elicited and required. NK cells, CD4+ T cells and interferon- γ were all found to be critical for tumor control while tumor infiltrating CD8+ T cells became disabled by an immunosuppressive microenvironment. There is potential for broader application of this cancer vaccine, as we have been able to demonstrate effectiveness in two additional cancer models; melanoma (B16-OVA) and a model of B cell lymphoma (E µ-myc-GFP-OVA).
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research